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  The microRNA-132 and microRNA-212 cluster regulates hematopoietic stem cell maintenance and survival with age by buffering FOXO3 expression.

Mehta, A., Zhao, J. L., Sinha, N., Marinov, G. K., Mann, M., Kowalczyk, M. S., et al. (2015). The microRNA-132 and microRNA-212 cluster regulates hematopoietic stem cell maintenance and survival with age by buffering FOXO3 expression. Immunity, 42(6), 1021-1032. doi:10.1016/j.immuni.2015.05.017.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-B0BC-0 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-721B-8
Genre: Journal Article

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 Creators:
Mehta, A., Author
Zhao, J. L., Author
Sinha, N., Author
Marinov, G. K., Author
Mann, M., Author
Kowalczyk, Monika S., Author
Galimidi, R.P., Author
Du, X., Author
Erikci, E.1, Author              
Regev, A., Author
Chowdhury, K.1, Author              
Baltimore, D., Author
Affiliations:
1Facility of Microarray Analyses, MPI for biophysical chemistry, Max Planck Society, ou_578589              

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 Abstract: MicroRNAs are critical post-transcriptional regulators of hematopoietic cell-fate decisions, though little remains known about their role in aging hematopoietic stem cells (HSCs). We found that the microRNA-212/132 cluster (Mirc19) is enriched in HSCs and is upregulated during aging. Both overexpression and deletion of microRNAs in this cluster leads to inappropriate hematopoiesis with age. Enforced expression of miR-132 in the bone marrow of mice led to rapid HSC cycling and depletion. A genetic deletion of Mirc19 in mice resulted in HSCs that had altered cycling, function, and survival in response to growth factor starvation. We found that miR-132 exerted its effect on aging HSCs by targeting the transcription factor FOXO3, a known aging associated gene. Our data demonstrate that Mirc19 plays a role in maintaining balanced hematopoietic output by buffering FOXO3 expression. We have thus identified it as a potential target that might play a role in age-related hematopoietic defects.

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Language(s): eng - English
 Dates: 2015-06-012015-06-16
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.immuni.2015.05.017
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Title: Immunity
Source Genre: Journal
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Pages: - Volume / Issue: 42 (6) Sequence Number: - Start / End Page: 1021 - 1032 Identifier: -